Myocardial cells divide very rapidly in the rat fetus. However, shortly after birth such proliferative rates slow markedly and for all practical purposes cease by the third to the sixth week after gestation. All further growth of the newborn heart into adulthood occurs by a process of myocardial cell enlargement, i.e., hypertrophy. The authors have shown in vitro that low intracellular oxygen tension greatly modifies the proliferative rates of many cell types, especially those of cardiac and skeletal muscle. They hypothesize that low tissue pO2 in the fetus could account for the rapid cell division in utero. The precipitous decline in the rate of mitosis after birth could be due to the more adequate oxygenation of the organism and higher tissue pO2. Our studies of the growth of cardiac and skeletal muscle in tissue culture lend support to this hypothesis. Low oxygen environments increase the rates of division of cardiac cells while progressively higher oxygen concentrations inhibit such cell proliferation. The present studies address themselves to various questions: Can the initial number of heart cells, with which the newborn animal is endowed, be increased in the first few weeks of life by lowering the ambient oxygen? Can stimulation of vascular endothelial cells by graded hypoxia endow the organism with a better capillary/muscle fiber ratio? If these can be achieved, then, can such increases in cell number protect him in adult life to withstand the stresses of experimentally induced (or clinically occurring) cardiac hypertrophy of myocardial ischemia? Pregnant rats and also newborn rats reared in chambers with 15 percent O2 will be compared with room air controls matched for body weight. Total RV or LV DNA and DNA concentrations will be measured (along with RNA and protein). H3 thymidine will be injected at various times during the first 21 days of life and labelling and mitotic indices measured for individual cell types (myocardial, fibroblast, vascular endothelium) as well as specific activities of DNA. Also, studies of skeletal muscle in culture will be continued to clarify the effects of O2 and pH on cell proliferation and differentiation.